Sabe-se que o vírus da imunodeficiência humana (HIV) pode modificar a história natural da infecção pelo HCV, acelerando a progressão da fibrose hepática e conseqüente evolução para cirrose. O tratamento com interferon-alfa pode levar à melhora da histologia hepática, reduzindo a inflamação e fibrose, principalmente nos pacientes que apresentam resposta virológica sustentada. O impacto do tratamento sobre a evolução histológica em pacientes não-respondedores ao tratamento da hepatite C apresenta resultados controversos. Objetivos: Avaliar, nos pacientes com hepatite C crônica, co-infectados pelo HIV, o impacto do tratamento da hepatite C, sobre as modificações de parâmetros indicativos de fibrose e atividade inflamatória, em biópsias de fígado realizadas antes e após o tratamento da hepatite C. Métodos: Foram estudados 26 pacientes co-infectados pelo HCV e HIV-1, submetidos à biópsia hepática antes e, em média, 25,2 meses após o término do tratamento da hepatite C. Fragmentos da biópsia hepática foram comparados, antes e após o tratamento, em relação aos seguintes parâmetros: Índice de Atividade Histológica (HAI) e o grau de Fibrose (Knodell); intensidade do depósito de colágeno (coloração pelo picrosirius) e o grau de ativação das células estreladas (marcação com alfa-actina de músculo liso). Os índices destas variáveis histológicas, pós e pré-tratamento, foram relacionadas com o resultado do teste qualitativo RNA HCV (RT-PCR-AMPLICOR?) na 24a semana de tratamento, com a duração do tratamento da hepatite C e com o intervalo de tempo entre a interrupção do tratamento e a biópsia-controle. Foi avaliada a relação de possíveis fatores prognósticos de resposta virológica com a resposta histológica e foram realizadas correlações dos parâmetros histológicos entre si. Resultados: Os parâmetros histológicos avaliados de forma global foram semelhantes nas biópsias pré e pós-tratamento. As razões pós/pré-tratamento, em todos os parâmetros avaliados nas biópsias hepáticas, diminuíram de forma significativa nos pacientes que apresentaram pesquisa negativa para o RNA HCV na 24ª semana de tratamento. Os parâmetros histológicos foram semelhantes nos grupos com duração de tratamentos diferentes (? 24 semanas e > 24 semanas), exceto as CEH células ?-positivas, que teve melhora no grupo com tratamento mais prolongado. O intervalo de tempo entre o final do tratamento e a biópsia-controle não influenciou a melhora histológica. Na análise de regressão logística, houve associação da melhora dos parâmetros histológicos com o resultado negativo do RNA HCV na 24ª semana de tratamento. Houve correlação significativa entre todos os parâmetros histológicos avaliados. Conclusões: Os pacientes avaliados em conjunto tiveram seus parâmetros histológicos nas biópsias pré e pós-tratamento com valores semelhantes, porém quando se definiu melhora histológica, como a manutenção, ou melhora dos parâmetros histológicos avaliados individualmente, verificou-se que uma substancial parcela da população estudada apresentou melhora histológica. O efeito benéfico do tratamento parece se relacionar com o controle da viremia do HCV durante o tratamento e se verifica também em pacientes que não sustentaram a resposta virológica após a suspensão dos medicamentos. Os achados fazem supor que a redução da viremia do HCV teria como conseqüência a diminuição da inflamação e fibrose hepáticas, inclusive com diminuição do estado de ativação das células estreladas hepáticas, mesmo nos casos em que não houve resposta virológica sustentada. Os resultados do presente estudo são sugestivos de que o tratamento da hepatite C pode modificar a história natural da evolução da hepatite crônica nos pacientes co-infectados pelo HIV. / Human immunodeficiency virus (HIV) is known to be able to modify the natural history of HCV infection, accelerating the progression of hepatic fibrosis and the consequent evolution to cirrhosis. Treatment with interferon-alpha can lead to improved hepatic histology, reducing inflammation and fibrosis, especially in patients who present a sustained virologic response. The impact of treatment on histological evolution in patients who do not respond to treatment of hepatitis C is a controversial matter. Objectives: To evaluate in patients with chronic hepatitis C co-infected with HIV the impact of treatment of hepatitis C on the modifications of the parameters indicative of fibrosis and of inflammatory activity in liver biopsies obtained before and after treatment of hepatitis C. Methods: Twenty-six patients co-infected with HCV and HIV-1 were submitted to a liver biopsy before and, on average, 25.2 months after the end of treatment of hepatitis C. Fragments of the liver biopsy were compared before and after treatment regarding the following parameters: histological activity index (HAI) and grade of fibrosis (Knodell); intensity of collagen deposition (picrosirius staining), and grade of stellate cell activation (labeling with smooth muscle alpha-actin). The post- and pretreatment ratios of these histological variables were related to the result of the quantitative HCV-RNA test (RT-PCR-AMPLICOR?) during the 24th week of treatment, to the duration of treatment of hepatitis C and to the time interval between the discontinuation of treatment and the control biopsy. The relationship between possible factors of the virologic response and the histological response was evaluated and correlations between the various histological parameters were calculated. Results: The histological parameters evaluated in a global manner were similar in the pre- and post-treatment biopsies. The post-pretreatment ratios for all parameters evaluated in the liver biopsies were significantly reduced in patients who were negative for HCV RNA during the 24th week of treatment. The histological parameters were similar in the groups with different durations of treatment (? 24 weeks and > 24 weeks), except for ?-positive stellate hepatic cells, which were improved in the group with a more prolonged treatment. The time interval between the end of treatment and the control biopsy did not affect the histological improvement. In logistic regression analysis, the improvement of the histological parameters was found to be associated with a negative result of HCV RNA during the 24th week of treatment. There was a significant correlation between all histological parameters evaluated. Conclusions: When evaluated as a whole, the patients showed similar values for their histological parameters in the pre- and post-treatment biopsies. However, when histological improvement was defined as the maintenance or improvement of the histological parameters evaluated individually, a substantial part of the study population was found to present histological improvement. The beneficial effect of treatment seemed to be related to the control of HCV viremia during treatment and was also observed in patients who did not sustain the virologic response after the discontinuation of the medications. These findings lead us to assume that the reduction of HCV viremia causes a reduction of hepatic inflammation and fibrosis, as well as a reduction of the state of activation of stellate hepatic cells even in cases in which there is no sustained virologic response. The results of the present study suggest that treatment of hepatitis C can modify the natural history of the course of chronic hepatitis in patients co-infected with HIV.

A implementação da integralidade é um grande desafio à consolidação do Sistema Único de Saúde e a vulnerabilidade na Atenção Básica às DST/HIV/aids foi o objeto deste estudo, cujos objetivos foram: caracterizar as Unidades Básicas de Saúde (UBS) segundo as Coordenadorias Regionais de Saúde, as Supervisões Técnicas de Saúde, os modelos de organização da atenção à saúde, as Organizações Sociais de Saúde em contratos de gestão na cogestão da saúde com a Secretaria Municipal de Saúde de São Paulo e a formação profissional do gerente; identificar o grau de Vulnerabilidade Programática das UBS e discuti-lo segundo os componentes: acessibilidade, porta de entrada, vínculo, enfoque familiar, profissionais da saúde e coordenação/integração. A perspectiva conceitual utilizada foi da vulnerabilidade, em sua dimensão programática. Realizou-se estudo descritivo transversal com abordagem quantitativa, tendo sido utilizado um questionário com 51 questões, aplicado online, na plataforma FormSUS, com gerentes das 442 UBS do Município de São Paulo. Foram obtidas respostas de 328 gerentes das UBS; 40,9% eram exclusivas \"tradicionais\"; 55,8% das OSS eram do tipo \"Associação\" e mais da metade dos gerentes das UBS eram Enfermeiros. Há graus diferenciados de vulnerabilidade programático, mas de um modo geral nas UBS é baixo. Há vulnerabilidade na efetivação da integralidade: falta de materiais para atividades educativas; baixa oferta de testes de detecção de sífilis à gestante e teste anti- HIV no pré-natal; demora no retorno do resultado do exame anti-HIV; baixa indicação do tratamento com Penicilina Benzatina ao parceiro da gestante com diagnóstico de sífilis; não realização da abordagem consentida para solicitação de teste para HIV à gestante ou para a população geral; falta de capacitação para realização da abordagem sindrômica das DST e aconselhamento na oferta do teste do HIV; falta de contrarreferência às UBS, DST/aids. Conclui-se que a integralidade traduzida em práticas de saúde na atenção às DST/HIV/aids possibilitou visualizar as vulnerabilidades programáticas nas UBS e apontou desafios para sua efetivação. / Implementation of comprehensive attention is a huge challenge in the consolidation of the Brazilian Unified Health System. The vulnerability to STD/HIV/Aids in Primary Care was focused on this study, aiming to provide tools to improve healthcare. The objectives of the study were: 1) to characterize Primary Care Units (PCU) according to selected variables such as: administrative hierarchy position (Regional Health Coordination, Healthcare Technical Supervision), administrative issues (models healthcare attention of organization, Healthcare Social Organization (HSO) in management or co-management with the Township Healthcare Office in São Paulo), and manager formal professional qualification; 2) to identify the level of Programmatic Vulnerability; and 3) to assess the Programmatic Vulnerability according to the following components: accessibility, point of entry, links, family approach, health professional and integration / coordination. The conceptual approach was the vulnerability in its programmatic dimension. This was a transversal descriptive and quantitative study based on an online survey with 51 questions applied in the FormSUS platform and involving managers from 442 PCU of the city of São Paulo. Responses were received from 328 PCU managers; among them more than half were Nurses. PCU were exclusively \"conventional in 40.9% and 55.8% of the HSO were classified as \"association\". There were different levels of programmatic vulnerability; in general however, the vulnerability was low. There was vulnerability in making comprehensive attention effective: lacking of material for educational activities; insufficiency of availability of tests to detect syphilis in pregnant women and anti-HIV test in the pre-natal period; excessive delay in results of anti-HIV tests causing them to be not time-opportune; low practice of indication of syphilis treatment with Benzathine Penicillin for the pregnant partner; lacking of informed consent to request HIV testing to pregnant women as well general population; lacking of training for the syndromic approach to STDs; lacking of counseling when offering HIV testing; lacking of counter-reference to PCU, STD/Aids. It was concluded that the translation of the comprehensiveness concept into health practices regarding STD/HIV/aids enabled us to assess programmatic vulnerabilities in the PCU, and pointed out challenges to achieve a true comprehensive healthcare attention.

Magister Public Health - MPH (Public Health) / The presence of highly effective medicines has made very little impact in reducing deaths as a result of tuberculosis (TB), a curable condition but when managed inappropriately, may result in Drug Resistant TB. TB accounts for about one in four deaths that occur in HIV positive people and HIV has been found to be a risk factor for complex unfavorable outcomes in MDR TB patients and a very strong predictor for death and default. The relationship between diabetes and TB has also been explored, with some authors identifying diabetes as a risk factor for TB, and with related poor clinical outcomes in both conditions when they co-exist. Exploring the clinical characteristics and treatment outcomes of MDR TB patients in the presence of these risk factors could present an opportunity to provide better care through increased case-detection activities, improved clinical management and better access to care for all these conditions. The aim of the study was to describe the clinical characteristics and treatment outcomes of MDR TB patients initiated on treatment at Nkqubela and Fort Grey Hospitals.

O Epstein-Barr Vírus (EBV) é um vírus da família Herpes (HHV-4), presente em grande parte da população mundial. É o agente etiológico da mononucleose infecciosa e da leucoplasia pilosa. A leucoplasia pilosa é uma doença epitelial benigna associada ao EBV, caracterizada pela reprodução replicativa do EBV nas células do epitélio oral, e é uma das mais freqüentes lesões oportunistas em pacientes HIV positivos, sendo menos freqüente apenas que a candidíase, com uma prevalência média entre 10 % e 30%. Por ser uma lesão oportunista bucal fortemente relacionada com a infecção pelo HIV e com a imunossupressão, seu diagnóstico é importante, pois pode sugerir o diagnóstico da infecção em pacientes de sorologia desconhecida para o HIV, e auxiliar no estadiamento da doença. Sua detecção e correto diagnóstico são de particular importância por essa condição estar relacionada à capacidade imune do paciente. Além disso, em pacientes já diagnosticados, ela é indicadora da progressão da doença e da eficácia da terapia antirretroviral. O objetivo desse estudo foi avaliar a presença e a quantidade do EBV na saliva e no sangue de pacientes infectados pelo HIV atendidos no CAPE-FOUSP, verificar a presença clínica de leucoplasia pilosa, estabelecendo a possibilidade da existência de vínculo entre a carga viral do EBV, a manifestação clínica da lesão e a carga viral do HIV. Também se buscou estabelecer relação entre o tipo de terapia antirretroviral em uso e a presença de leucoplasia pilosa, bem como estabelecer relação entre a carga viral do EBV na saliva e no sangue. Foram analisadas 20 lesões de leucoplasia pilosa, num total de 94 pacientes avaliados. Foi encontrada uma correlação positiva entre a Carga Viral do EBV no sangue e na saliva (p=0,001). Quanto maior a carga viral no sangue, maior a carga viral na saliva. Foi encontrada associação entre a Carga Viral do EBV na saliva e a presença de Leucoplasia Pilosa (p=0,045). Indivíduos com Leucoplasia Pilosa apresentam maior Carga Viral de EBV na saliva do que indivíduos sem essa lesão. Foi encontrada uma correlação positiva entre a Carga Viral do HIV e a Carga Viral do EBV na saliva (p=0,006) porém não no sangue. Quanto maior a carga viral de HIV, maior a carga viral do EBV na saliva. Foi encontrada correlação positiva entre a Carga Viral do EBV no sangue e as contagens de CD4 mais baixa registrada e a mais atual (p=0,028 e p=0,030 respectivamente). Quanto maior Carga Viral do EBV no sangue, maior a contagem de CD4. Não foi encontrada associação entre o tipo de medicação antirretroviral em uso e presença de lesão de leucoplasia pilosa. / The Epstein-Barr Virus (EBV) is a herpes virus family (HHV-4), is present in great part of the world population. It is the causative agent of infectious mononucleosis and oral hairy leukoplakia. Oral hairy leukoplakia is a benign epithelial disease associated with EBV, which is characterized by the replicative reproduction of EBV in oral epithelial cells, and is one of the most frequent opportunistic lesions in HIV positive patients, only less frequent than candidiasis, with an average prevalence between 10% and 30%. Being an opportunistic oral lesion strongly associated with HIV infection and immunosuppression, its diagnosis is important, because it may suggests the diagnosis of infection in patients of unknown HIV serology, and assist in the staging of the disease. Its detection and correct diagnosis are particularly important because this condition is related to the patient\'s immune capacity. Moreover, in patients already diagnosed, it is indicative of disease progression and effectiveness of antiretroviral therapy. The aim of this study was to evaluate the presence and quantity of EBV in saliva and blood of HIV-infected patients treated at the CAPE-FOUSP, verifying the presence of clinical OHL, establishing the possibility of the existence of a link between viral load and EBV, clinical manifestation of the lesion, and HIV viral load. It was also aimed to establish the relationship between the type of antiretroviral therapy in use and the presence of oral hairy leukoplakia, as well as establish the relationship between viral load of EBV in saliva and blood. We analyzed 20 lesions of oral hairy leukoplakia, a total of 94 patients. Found a positive correlation between viral load of EBV in blood and saliva (p = 0.001). The higher the viral load in blood, the higher the viral load in saliva. Association was found between viral load of EBV in saliva and the presence of oral hairy leukoplakia (p = 0.045).Individuals with oral hairy leukoplakia have a higher viral load of EBV in saliva than those without such injury. Found a positive correlation between viral load and HIV viral load of EBV in saliva (p = 0.006) but not in blood. The higher the viral load of HIV, the higher the viral load of EBV in saliva. A positive correlation was found between viral load of EBV in blood and CD4 counts the lowest recorded and most current (p = 0.028 and p = 0.030 respectively). The higher viral load of EBV in blood, increased CD4 count. No association was found between the type of antiretroviral medications in use and presence of oral hairy leukoplakia lesions.

Magister Psychologiae - MPsych / Globally, and especially in Sub-Saharan Africa the advent of HIV and AIDS has created new inequalities within already challenged health care systems. Chronic illnesses have often been associated with increased prevalence of psychological symptoms. Both national and international studies have found a strong association between psychiatric morbidity and HIV and AIDS. Furthermore, studies have found that social support contributes to positive adjustment of individuals infected with HIV and provides a buffer against the effects of anxiety. The aim of this study was therefore to examine anxiety and social support in adults diagnosed with HIV or AIDS at a public health clinic in the Western Cape. The objectives in relation to the aim were: (1) To determine the prevalence of anxiety in adults diagnosed with HIV or AIDS. (2) To determine the degree of social support, as a component of quality of life,in adults diagnosed with HIV or AIDS. (3) To examine the relationship between anxiety and social support in adults diagnosed with HIV or AIDS. The broad theoretical framework that guides this study is the bio-psycho-social model. A cross-sectional design was used in which 70 participants were recruited using a purposive sampling method. Participants were assessed using well-validated self-administered questionnaires: Hospital Anxiety and Depression Scale(HADS) and Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q). Data were analysed using the Statistical Package for the Social Sciences (SPSS) version 17.1. Correlational and inferential statistics were conducted. The findings of this study indicated that participants in this study had higher levels of anxiety (28%) when compared to the general population (15.8%). Participants in this study, indicated a 59% enjoyment and satisfaction with social support, which indicates satisfaction with social support some of the time. There was however no significant relationship between anxiety and social support in this study. HIV intervention efforts should include screening HIV positive individuals for the presence of psychiatric symptoms. Interventions should also include encouraging HIV positive individuals to maintain and expand their social networks.

Magister Public Health - MPH / The reproductive health of women is hugely dependent on the involvement of their male partners. Men also serve as gatekeepers to women’s access to reproductive health services. Male involvement is an important recommendation for the Prevention of Mother-to-Child Transmission of HIV (PMTCT) program as their participation in antenatal care and HIV testing has been found to decrease infant HIV infection and increase HIV free survival. Male involvement is not just about promoting men to accompany their partners to antenatal clinic, but for men to provide supportive roles in their families, and also to bring men into HIV preventive and care services. Male involvement in PMTCT is defined as the fathers’ active involvement in attending antenatal care services and HIV testing during the antenatal period as well as the couple’s acceptance of PMTCT if the mother is found to be HIV positive. Men are traditionally not directly involved in their partner’s health in many sub-Saharan countries, although they most often make decisions about use of services. They may provide financial support but attending health services with their partner is not seen as part of the male’s role. There are therefore huge challenges in efforts to get men involved in reproductive health services and there is a need to better understand how to promote male involvement in different settings. Male involvement in PMTCT was adopted by the Zambian Government in 1999 but not much is known on how best to initiate and develop male involvement in their partner’s health.

Les Contrôleurs du VIH sont de rares individus capables de contrôler spontanément la réplication virale en l’absence de traitement. De nombreuses études montrent que les Contrôleurs développent des réponses T antivirales remarquablement efficaces. Les cellules T CD4+ spécifiques de Gag pourraient jouer un rôle particulier car cette population est préservée en comparaison aux patients traités et corrèle négativement avec la charge virale. Afin d’étudier cette population, nous avons réalisé une analyse transcriptionnelle et protéique multiplexée sur cellule unique, à partir de cellules T CD4+ détectées ex vivo par marquage tétramère de CMH-II contre le peptide Gag293 (Tet+). Nous avons comparé l’expression de 44 gènes et 6 protéines membranaires chez 9 patients Contrôleurs et 9 patients traités. Nous avons d’une part validé la forte fréquence de cellules T CD4+ Tet+ chez les Contrôleurs en comparaison aux patients traités et, d’autre part, montré que les cellules T CD4+ Tet+ des Contrôleurs, étaient activées et engagées dans une différenciation Th1 avancée et présentant un profil cytotoxique. De plus, les cellules T CD4+ Tet+ de Contrôleurs ont montré un état d’épuisement limité, reflété par une expression faible de PD-1, qui pourrait être l’une des raisons du maintien de leur fréquence et de leurs fonctions. Dans une deuxième étude, nous avons étudié les cellules T folliculaires « helper » (Tfh) dans la population T CD4+ spécifique de Gag chez les Contrôleurs du VIH. Les Tfh jouent un rôle essentiel dans la maturation d’affinité des anticorps en aidant les cellules B. Afin de déterminer si ce sous-type cellulaire joue un rôle dans le contrôle de l’infection à VIH, nous avons analysé le phénotype et la fonction des Tfh circulantes (cTfh) : cellules T CD4+ CD45RA- CXCR5+). Nous avons utilisé un marquage tétramère de CMH-II contre le peptide Gag293, pour détecter les cTfh spécifiques du VIH (cTfh Tet+), et nous avons montré que cette population est préférentiellement maintenue chez les Contrôleurs du VIH. L’analyse phénotypique de la population cTfh Tet+ a montré une intensité d’expression (MFI) de PD-1 plus importante dans le groupe de patients traités, suggérant une activation immune anormale chez ces patients. La fonction des cTfh, analysée pour leur capacité à induire la sécrétion d’IgG en coculture avec des cellules B mémoires autologues, n’a pas montré de différences majeures entre les groupes en terme de production d’IgG totales. Cependant, la production d’IgG spécifiques anti-VIH est significativement plus efficace chez les Contrôleurs, en particulier pour la réponse anti-Env qui est plus de 30 fois supérieure à celle des patients traités. Enfin, la fréquence des cTfh Tet+ a corrélé positivement avec la production d’IgG spécifiques, supportant l'idée d'un rôle important de la fonction Tfh dans la réponse humorale anti-VIH. L’ensemble de ces résultats indique que la population T CD4+ spécifique de Gag supporte chez les Contrôleurs les deux bras de la réponse immunitaire antivirale : d’une part, une réponse de type cellulaire Th1 montrant un profil cytotoxique et, d’autre part, une réponse de type humorale, reflétée par des interactions cTfh/B préservées, résultant en une réponse B mémoire vigoureuse. Le maintien de la fonction et de la fréquence de ces cellules spécifiques de Gag pourrait donc jouer un rôle important dans le contrôle du VIH / HIV Controllers are rare individuals able to spontaneously control viral replication in the absence of treatment. Several studies showed that controllers develop effective anti-viral T cell responses. Gag-specific CD4+ T cells could play a particular role in HIV control, because this population is preserved in comparison with the treated patients and correlates negatively with the viral load. In order to study this population, we performed a multiplexed single cell transcriptional and protein analysis from CD4+ T cells detected ex vivo by MHC-II tetramer labeling against the Gag293 peptide (Tet+). We compared the expression of 44 genes and 6 surface proteins in 9 Controllers patients and 9 treated patients. Firstly, we validated the high frequency of Tet+ CD4+ T cells in controllers compared to the treated patients, then we showed that Tet+ CD4+ T cells from controllers were activated and engaged in advanced Th1 differentiation with a cytotoxic profile. In addition, Tet+ CD4+ T cells from controllers showed a limited state of exhaustion, reflected by a lower expression of PD-1, which could be one of the reasons for maintaining their frequency and functions. In a second study, we studied follicular helper T cells (Tfh) among the Gag-specific CD4+ T cell population of HIV controllers. Tfh plays an essential role in the affinity maturation of the antibody response by providing help to B cells. To determine whether this CD4+ T cell subset may contribute to the spontaneous control of HIV infection, we analyzed the phenotype and function of circulating Tfh (cTfh: T cells CD4+ CD45RA- CXCR5+). We performed a MHC-II tetramer labeling against Gag293 peptide to detect HIV-specific cTfh (cTfh Tet +), and showed that this population is preferentially maintained in HIV controllers. Phenotypic analysis of Tet+ cTfh population showed a higher intensity of PD-1 expression (MFI) in the treated group suggesting abnormal immune activation in these patients. The function of cTfh, analyzed by the capacity to promote IgG secretion in cocultures with autologous memory B cells, did not show major differences between groups in terms of total IgG production. However, the production of HIV-specific IgG is significantly more efficient in the controller group, especially for the anti-Env response that is more than 30-fold greater than those of the treated patients. Finally, the frequency of Tet+ cTfh correlated positively with the production of specific IgG, supporting the idea of an important role of Tfh function in the humoral antiHIV response. Taken together, these results indicate that Gag-specific CD4+ T cell population supports the two arms of the antiviral immune response in HIV controllers: the cell-mediated response through a preferential differentiation toward Th1 cell type showing a cytotoxic profile, and the humoral response, reflected by preserved cTfh / B interactions, resulting in a vigorous memory response. Maintaining the function and frequency of these Gag-specific CD4+ T cells could therefore play an important role in HIV control

<p>Antiretroviral regimens have side effects that can threaten adherence by patients resulting in evolution of viral resistance due to suboptimal drug levels. Studies have shown that drug adherence of at least 80% can result in viral load suppression. There is no literature on the association between the level of adherence to antiretroviral therapy and the degree of virological suppression in Namibia. The aim of the present study was to determine the therapeutic and virological outcomes in HIV/AIDS patients at 6 and 12 months after initiation of highly-active antiretroviral therapy (HAART) in an urban population in Namibia. The distribution of viral load results showed a low uptake (35%) of virological monitoring at 6 month time point and even lower (12%) at 12 months. A conservative viral load threshold for virological response is required in the Namibian setting. The current adherence level of &gt / 80% encourage increased ARV therapy rollout. Poor virological outcome was associated with self-reported adherence.</p>

There is a growing interest in the dynamics of the co-infection of these two diseases. In this thesis, firstly we focus on studying the effect of a distributed delay representing the incubation period for the malaria parasite in the mosquito vector to possibly reduce the initial transmission and prevalence of malaria. This model can be regarded as a generalization of SEI models (with a class for the latently infected mosquitoes) and SI models with a discrete delay for the incubation period in mosquitoes. We study the possibility of occurrence of backward bifurcation. We then extend these ideas to study a full model of HIV and malaria co-infection. To get further inside into the dynamics of the model, we use the geometric singular perturbation theory to couple the fast and slow models from the full model. Finally, since the governing models are very complex, they cannot be solved analytically and hence we develop and analyze a special class of numerical methods to solve them.

In this thesis, we study these models and design and analyze robust numerical methods to solve them. To proceed in this direction, first we study the sub-models and then the full model. The first sub-model describes the transmission dynamics of HIV that accounts for behavior change. The impact of HIV educational campaigns is also studied. Further, we explore the effects of behavior change and different responses of individuals to educational campaigns in a situation where individuals may not react immediately to these campaigns. This is done by considering a distributed time delay in the HIV sub-model. This leads to Hopf bifurcations around the endemic equilibria of the model. These bifurcations correspond to the existence of periodic solutions that oscillate around the equilibria at given thresholds. Further, we show how the delay can result in more HIV infections causing more increase in the HIV prevalence. Part of this study is then extended to study a co-infection model of HIV-TB. A thorough bifurcation analysis is carried out for this model. Robust numerical methods are then designed and analyzed for these models. Comparative numerical results are also provided for each model.